Lung-Brain Axis Mechanisms of Cognitive Dysfunction in Long COVID.

Abstract

Cognitive dysfunction, characterized by memory impairment, attentional deficits, and executive dysfunction, represents a critical clinical manifestation in post-acute sequelae of COVID-19 that significantly compromises patients' quality of life. The lung-brain axis, as a bidirectional regulatory network connecting the respiratory system to the central nervous system, interacts through neural circuits, humoral pathways, and microbial pathways, and may play a central role in the cognitive impairments occurring in long COVID (LC). This paper systematically reviews the multidimensional pathways of the lung-brain axis and their pathological mechanisms in the cognitive impairment of LC, including direct viral neuroinvasion during the acute phase, chronic injury triggered by viral persistence, immune homeostasis dysregulation, hypoxaemia, microbiome disruption, and renin- angiotensin system imbalance. It then explores clinical intervention strategies based on the lungbrain axis, integrating supportive treatments, such as oxygen therapy, exercise therapy, and cognitive training, with treatments targeting the lung-brain axis, including antiviral drugs, immunomodulation, probiotics, and neuromodulation techniques. It is also suggested that future research should favour the integration of multi-omics technologies and the development of individualised therapeutic targets.